CA1296022C - Preparation of o-substituted hydroxylamine hydrochlorides - Google Patents
Preparation of o-substituted hydroxylamine hydrochloridesInfo
- Publication number
- CA1296022C CA1296022C CA000546726A CA546726A CA1296022C CA 1296022 C CA1296022 C CA 1296022C CA 000546726 A CA000546726 A CA 000546726A CA 546726 A CA546726 A CA 546726A CA 1296022 C CA1296022 C CA 1296022C
- Authority
- CA
- Canada
- Prior art keywords
- hydrogen chloride
- preparation
- acetoxime
- substituted hydroxylamine
- ether
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
- C07C239/08—Hydroxylamino compounds or their ethers or esters
- C07C239/20—Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Abstract of the Disclosure: O-substituted hydroxylamine hydrochlorides I
R-O-NH2 . HCl (I) where R is C1-C4-alkyl, C3- or C4-alkenyl, C3- or C4-haloalkenyl or benzyl, are prepared by continuous hydroly-sis of the corresponding acetoxime ethers II
R-O-NH2 . HCl (I) where R is C1-C4-alkyl, C3- or C4-alkenyl, C3- or C4-haloalkenyl or benzyl, are prepared by continuous hydroly-sis of the corresponding acetoxime ethers II
Description
- 1 - O.Z. 0050/38679 Preparation of 0-substituted hydroxylamine hydrochlorides The present invention relates to a novel process for the preparation of 0-substituted hydroxylamine hydrochlorides of the formula I
R 0-NHz . HCl (I) where R ;s C1-C4-alkyl, C3- or C4-alkenyl, C3- or C4-haloalkenyl or benzyl.
A large number of methods are known for the preparation of O-substituted hydroxylamines, but the methocls are technically and economically unsa~isfactory.
In particular, Houben-Weyl, Methoden der organis-chen Chemie, Volume 10/1, 4th Edition, 1971, 1186-1189, discloses that certain aldoxime and ketoxime ethers can be hydrolyzed with mineral acids to give the correspond-ing salts of 0-substituted hydroxylamine; however, the yields o~tainable are unsa~isfactory.
It is an object of the present invention to make the 0-substituted hydro~ylamines I which are important for the synthesis of drugs and crop protection agents more readily available technically and economicaLly.
~ e have found that this object is achieved by a process for the preparation of 0-substituted hydroxylamine hydrochlor;des of the general formula I
R-0-NHz . HCl ~I) where R is C1-C4-alkyl~ C3- or C4-alkenyl, C3- or C4-haloalkenyl or benzyl, by cleaving the corresponding acetoxime ether of the general formula II
CH3 ( I I ), R--O--N=C~
wherein, according to the invention, the cleavage is carried out continuously in a reaction column contain-ing not less than Z0 theoretical plates with constant removal o~ the acetone eliminated, using hydrogen chloride and water.
~2~2~
R 0-NHz . HCl (I) where R ;s C1-C4-alkyl, C3- or C4-alkenyl, C3- or C4-haloalkenyl or benzyl.
A large number of methods are known for the preparation of O-substituted hydroxylamines, but the methocls are technically and economically unsa~isfactory.
In particular, Houben-Weyl, Methoden der organis-chen Chemie, Volume 10/1, 4th Edition, 1971, 1186-1189, discloses that certain aldoxime and ketoxime ethers can be hydrolyzed with mineral acids to give the correspond-ing salts of 0-substituted hydroxylamine; however, the yields o~tainable are unsa~isfactory.
It is an object of the present invention to make the 0-substituted hydro~ylamines I which are important for the synthesis of drugs and crop protection agents more readily available technically and economicaLly.
~ e have found that this object is achieved by a process for the preparation of 0-substituted hydroxylamine hydrochlor;des of the general formula I
R-0-NHz . HCl ~I) where R is C1-C4-alkyl~ C3- or C4-alkenyl, C3- or C4-haloalkenyl or benzyl, by cleaving the corresponding acetoxime ether of the general formula II
CH3 ( I I ), R--O--N=C~
wherein, according to the invention, the cleavage is carried out continuously in a reaction column contain-ing not less than Z0 theoretical plates with constant removal o~ the acetone eliminated, using hydrogen chloride and water.
~2~2~
- 2 - o.z. 0050/38679 R is, for example, - C1-C4-alkyl, ie. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl, - C3- or C4-alkenyl, such as prop-2-enyl, but-Z-enyl and but-3-enyl, - C3- or C4-haloalkenyl, such as 3-chloroprop-2-enyl, 2-chloroprop-2-enyl, 2-chlorobut-Z-enyl, 3-chlorobut-2-enyl, 2,3-dichloroprop-2-enyl, 2,3-dichlorobut-2-enyl, 3-bromoprop-2-enyl, 3-fluoroprop-2-enyl, 2-bromoprop-2-enyl, 2-fluoroprop-2-enyl, 2,3-dibromoprop-2-enyl and 2,3-dibromobut-2-enyl, or - benzyl~
The starting compounds II are known or are obtain-able by known methods, for example by ether;fication of acetoxime (German Laid-Open Applications DOS 2,9Z7,117, EP-A-121 701 and EP-A-158 159).
Regard;ng the convers;on of the acetoxime ethers II to the O-subst;tuted hydroxylamine hydrochlorides I, the following may be stated:
Part;cularly suitable reaction columns are tray columns of any design, especially bubble cap columns, since the res;dence t;mes on the trays can be readily ad-justed in these columns. Packed columns are also su;t-able. The number of theoretical plates ;s generally from ZO to 60, preferably from 30 to 50, although the upper lim;t for the number of plates ;s determ;ned only by : econom;c cons;derations.
The hydrogen chlor;de required for the hydroly-s;s ;s preferably used ;n a sto;ch;ometr;c amount, al-though it is also poss;ble to use an excess, for exam-ple up to 1 mole per mole of acetox;me ether II.
Where aqueous hydrochlor;c acid ;s used, its con-centration ;s preferably from 10 to 20, in part;cular from 15 to 20, % by we;ght.
In a preferred embodiment, the procedure can be carr;ed out ;n the presence of 1,4-dioxane, from wh;ch the hydroxylamine I can readily be obtained in crystalline ~.2~ ~
form. In this case, however, the amount of water used must be as small as possible (i.e. 1 to 1.6 mole water ~or 1 mole acetoxime ether II) and furthermore hydrogerl chloride must therefore be used in gaseous form.
Otherwise, the reactant II, a solution of lI, water and hydrogen chloride or aqueous hydrochloric acid are advantageously fed in at the middle of the column, and the feed rate and heating power are chosen so that the mean residence time in the co~umn is from 3 to 4 hours.
The general rule ~ith regard to the feed point is that compounds II having a higher boiling point are introduced at a higher tray than those having a ~ow boiling point.
The reaction temperature is advantageously from 70 to 140C, so that the procedure can be carried out under atmospheric pressure; if necessary, slightly reduced pressure down to about SûO mbar or slightly superatmospheric pressure up to about 3 bar may be used. The acetone taken off con-tinuously at the top at a reflux ratio of, for example, ; from 1:5 to 1.50, preferably from 1:5 to 1:20, can be re-used for the preparation of acetoxime ether II.
At the bottom of the coLumn, an aqueous solution of O-substituted hydroxylamine hydrochloride I or a sus-pension of I in 1,4-dioxane is obtained.
This solution or suspension is discharged continuous-ly and, if necessary, is worked up to give the pure pro-ducts I in a conventional manner by crystallization or by stripping off the liquid.
This gives the compounds I in a purity and in a yield high enough to permit them to be used directly for syntheses.
The O-substituted hydroxylamine hydrochlorides are useful intermediates for the preparation of drugs and crop protection agents.
Preparation of the O-substituted hydroxylamine hydro-chlorides l ; 131.2 9 of acetGxime ethyl ether in 237.5 9 o;
~2~ 2 4 - O.Z. 0050t38679 1,4-dioxane, 31.3 9 of water and 47.3 9 of hydrogen chloride were metered in, per hour, at the 30th tray of a bubble cao column which contained 60 trays, had an internal diameter of 50 mm and was equiPped with a thin film evaporator and an automa~ic reflux divider. Acetone was taken off at the top at a reflux ratio of 1:15, and the dioxane/product mixture was removed as a bottom product. The latter was filtered off under suction and the solid dried under reduced pressure.
123.0 g/h (97% yield) of ethoxyamine hydrochloride (Compound 1) of melting point 133C were obtained.
In the apparatus described above, 139.9 g/h of acetoxime trans-crotyl ether and 315 g/h of 1,4-dioxane were metered in at the 50th tray~ 40.1 g/h of hydrogen chloride were metered in at the 20th tray and 25.8 g/h of water were metered in at the 30th tray. Acetone was taken off at the top at a reflux ratio of 1:16. After cool;ng, the product was filtered off under suction and dr;ed under reduced pressure.
126.4 g/h (93% yield) of trans-crotyloxyamine hydrochloride (Compound 2) of melt;ng point 169C were obtained.
The 0-subst;tuted hydroxylamine hydrochlorides listed in Table 1 were obta;ned ~rom the corresponding acetoximes II, sim;larly to Examples 1 and 2:
HzN-O-R . HCl (I) Compound _ _R _ _ _ mp. [C~ r;eld %
3û 4 (cH2)2cH3 154 95 (CH2)3CH3 153 93 6 CH2CH(CH3)2 129 92 7 (CH2)4CH3 149 91 8 CH2CH=CH2 168 94 9 trans-CH2 CH=CHCl 180 92 CH2c(cH3)=cH2 165 91 11 CH~gH5 - ~ 225 _ 91 CI 2~
The starting compounds II are known or are obtain-able by known methods, for example by ether;fication of acetoxime (German Laid-Open Applications DOS 2,9Z7,117, EP-A-121 701 and EP-A-158 159).
Regard;ng the convers;on of the acetoxime ethers II to the O-subst;tuted hydroxylamine hydrochlorides I, the following may be stated:
Part;cularly suitable reaction columns are tray columns of any design, especially bubble cap columns, since the res;dence t;mes on the trays can be readily ad-justed in these columns. Packed columns are also su;t-able. The number of theoretical plates ;s generally from ZO to 60, preferably from 30 to 50, although the upper lim;t for the number of plates ;s determ;ned only by : econom;c cons;derations.
The hydrogen chlor;de required for the hydroly-s;s ;s preferably used ;n a sto;ch;ometr;c amount, al-though it is also poss;ble to use an excess, for exam-ple up to 1 mole per mole of acetox;me ether II.
Where aqueous hydrochlor;c acid ;s used, its con-centration ;s preferably from 10 to 20, in part;cular from 15 to 20, % by we;ght.
In a preferred embodiment, the procedure can be carr;ed out ;n the presence of 1,4-dioxane, from wh;ch the hydroxylamine I can readily be obtained in crystalline ~.2~ ~
form. In this case, however, the amount of water used must be as small as possible (i.e. 1 to 1.6 mole water ~or 1 mole acetoxime ether II) and furthermore hydrogerl chloride must therefore be used in gaseous form.
Otherwise, the reactant II, a solution of lI, water and hydrogen chloride or aqueous hydrochloric acid are advantageously fed in at the middle of the column, and the feed rate and heating power are chosen so that the mean residence time in the co~umn is from 3 to 4 hours.
The general rule ~ith regard to the feed point is that compounds II having a higher boiling point are introduced at a higher tray than those having a ~ow boiling point.
The reaction temperature is advantageously from 70 to 140C, so that the procedure can be carried out under atmospheric pressure; if necessary, slightly reduced pressure down to about SûO mbar or slightly superatmospheric pressure up to about 3 bar may be used. The acetone taken off con-tinuously at the top at a reflux ratio of, for example, ; from 1:5 to 1.50, preferably from 1:5 to 1:20, can be re-used for the preparation of acetoxime ether II.
At the bottom of the coLumn, an aqueous solution of O-substituted hydroxylamine hydrochloride I or a sus-pension of I in 1,4-dioxane is obtained.
This solution or suspension is discharged continuous-ly and, if necessary, is worked up to give the pure pro-ducts I in a conventional manner by crystallization or by stripping off the liquid.
This gives the compounds I in a purity and in a yield high enough to permit them to be used directly for syntheses.
The O-substituted hydroxylamine hydrochlorides are useful intermediates for the preparation of drugs and crop protection agents.
Preparation of the O-substituted hydroxylamine hydro-chlorides l ; 131.2 9 of acetGxime ethyl ether in 237.5 9 o;
~2~ 2 4 - O.Z. 0050t38679 1,4-dioxane, 31.3 9 of water and 47.3 9 of hydrogen chloride were metered in, per hour, at the 30th tray of a bubble cao column which contained 60 trays, had an internal diameter of 50 mm and was equiPped with a thin film evaporator and an automa~ic reflux divider. Acetone was taken off at the top at a reflux ratio of 1:15, and the dioxane/product mixture was removed as a bottom product. The latter was filtered off under suction and the solid dried under reduced pressure.
123.0 g/h (97% yield) of ethoxyamine hydrochloride (Compound 1) of melting point 133C were obtained.
In the apparatus described above, 139.9 g/h of acetoxime trans-crotyl ether and 315 g/h of 1,4-dioxane were metered in at the 50th tray~ 40.1 g/h of hydrogen chloride were metered in at the 20th tray and 25.8 g/h of water were metered in at the 30th tray. Acetone was taken off at the top at a reflux ratio of 1:16. After cool;ng, the product was filtered off under suction and dr;ed under reduced pressure.
126.4 g/h (93% yield) of trans-crotyloxyamine hydrochloride (Compound 2) of melt;ng point 169C were obtained.
The 0-subst;tuted hydroxylamine hydrochlorides listed in Table 1 were obta;ned ~rom the corresponding acetoximes II, sim;larly to Examples 1 and 2:
HzN-O-R . HCl (I) Compound _ _R _ _ _ mp. [C~ r;eld %
3û 4 (cH2)2cH3 154 95 (CH2)3CH3 153 93 6 CH2CH(CH3)2 129 92 7 (CH2)4CH3 149 91 8 CH2CH=CH2 168 94 9 trans-CH2 CH=CHCl 180 92 CH2c(cH3)=cH2 165 91 11 CH~gH5 - ~ 225 _ 91 CI 2~
- 5 - O.Z. 0050/38679 In the bubble cap column described in Example 1, 113~3 g/h of acetoxime methyl ether were metered in at the 10th tray and 262.8 g/h of 18% strength a~ueous hydro-S chloric acid were metered in at the 40th tray. Acetonewas taken off at the top at a reflux ratio of 1:8, and the aqueous solution of the product was removed as a bot-tom product. 30009 g/h of a 3S% strength solution of methoxyamine hydrochloride (Compound 3) (^105.3 g/h of dry substance, 97% yield) were obtained.
The O-subst;tuted hydroxylamines I listed in Table 2 were obtained in the form of their hydrochlorides in aqueous solution, from the corresponding acetoxime ethers II, similarly to Example 3:
CH2N-O-R . Hcl]aq (I) Compound R _ Yield %
8 CHzCH=CH2 _ ~ _ _3
The O-subst;tuted hydroxylamines I listed in Table 2 were obtained in the form of their hydrochlorides in aqueous solution, from the corresponding acetoxime ethers II, similarly to Example 3:
CH2N-O-R . Hcl]aq (I) Compound R _ Yield %
8 CHzCH=CH2 _ ~ _ _3
Claims (4)
1. A process for the preparation of an O-substituted hydroxylamine hydrochloride of the formula I
R-O-NH2 ? HCl (I) where R is C1-C4-alkyl, C3- or C4-alkenyl, C3- or C4-haloalkenyl or benzyl, by cleaving a correspanding acet-oxime ether of the formula II
(II), wherein the cleavage is carried out continuously in a re-action column containing not less than 20 theoretical plates with constant removal of the acetone eliminated, using hydrogen chloride and water.
R-O-NH2 ? HCl (I) where R is C1-C4-alkyl, C3- or C4-alkenyl, C3- or C4-haloalkenyl or benzyl, by cleaving a correspanding acet-oxime ether of the formula II
(II), wherein the cleavage is carried out continuously in a re-action column containing not less than 20 theoretical plates with constant removal of the acetone eliminated, using hydrogen chloride and water.
2. A process as claimed in claim 1, wherein the cleavage is carried out using a stoichiometric amount of hydrogen chloride and acetoxime ether II.
3. A process as claimed in claim 1, wherein the hydrogen chloride is used in the form of 10-20% strength by weight hydrochloric acid.
4. A process as claimed in claim 1, wherein the hydrolysis is carried out in 1,4-dioxane as the solvent, with from 1 to 1.6 moles of water per mole of acetoxime ether II and while passing in hydrogen chloride gas.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19863631071 DE3631071A1 (en) | 1986-09-12 | 1986-09-12 | METHOD FOR PRODUCING O-SUBSTITUTED HYDROXYLAMINE HYDROCHLORIDES |
| DEP3631071.9 | 1986-09-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1296022C true CA1296022C (en) | 1992-02-18 |
Family
ID=6309445
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000546726A Expired - Lifetime CA1296022C (en) | 1986-09-12 | 1987-09-11 | Preparation of o-substituted hydroxylamine hydrochlorides |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0259850B1 (en) |
| JP (1) | JPH07108890B2 (en) |
| AT (1) | ATE65244T1 (en) |
| CA (1) | CA1296022C (en) |
| DE (2) | DE3631071A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103113257A (en) * | 2013-03-08 | 2013-05-22 | 福州大学 | Continuous reactive distillation equipment for synthesising methoxylamine hydrochloride and process thereof |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4233333A1 (en) * | 1992-10-05 | 1994-04-07 | Basf Ag | Process for the preparation of O-substituted hydroxylammonium salts |
| US5393921A (en) * | 1993-07-07 | 1995-02-28 | The Gillette Company | Process for synthesizing O-substituted oxime compounds and conversion to the corresponding O-substituted hydroxylamine |
| DE59405913D1 (en) * | 1993-07-31 | 1998-06-10 | Basf Ag | METHOD FOR PRODUCING O-SUBSTITUTED HYDROXYLAMMONIUM SALTS |
| US5488162A (en) * | 1994-01-03 | 1996-01-30 | Buckland; Paul R. | Process for preparing o-alkylhydroxylamine salts without the isolation of intermediates |
| US5777164A (en) * | 1997-04-14 | 1998-07-07 | Eastman Chemical Company | Process for the preparation of high purity O-substituted hydroxylamine derivatives |
| DE19911234A1 (en) * | 1999-03-15 | 2000-09-28 | Basf Ag | Process for the continuous production of methoxyamine hydrochloride |
| JP2002039836A (en) * | 2000-07-21 | 2002-02-06 | Nippon Soda Co Ltd | Interlayer liquid level controlling method in sequential extraction |
| CN110606813A (en) * | 2019-09-17 | 2019-12-24 | 浙江圣安化工股份有限公司 | Oxime ether containing active group and synthetic method thereof |
| CN113636953B (en) * | 2021-08-16 | 2024-04-19 | 诚弘制药(威海)有限责任公司 | Preparation method of O-/N-alkyl substituted hydroxylamine salt |
-
1986
- 1986-09-12 DE DE19863631071 patent/DE3631071A1/en not_active Withdrawn
-
1987
- 1987-09-09 DE DE8787113161T patent/DE3771423D1/en not_active Expired - Lifetime
- 1987-09-09 JP JP62224217A patent/JPH07108890B2/en not_active Expired - Lifetime
- 1987-09-09 AT AT87113161T patent/ATE65244T1/en not_active IP Right Cessation
- 1987-09-09 EP EP87113161A patent/EP0259850B1/en not_active Expired - Lifetime
- 1987-09-11 CA CA000546726A patent/CA1296022C/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103113257A (en) * | 2013-03-08 | 2013-05-22 | 福州大学 | Continuous reactive distillation equipment for synthesising methoxylamine hydrochloride and process thereof |
| CN103113257B (en) * | 2013-03-08 | 2015-04-15 | 福州大学 | Continuous reactive distillation equipment for synthesising methoxylamine hydrochloride and process thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE65244T1 (en) | 1991-08-15 |
| DE3631071A1 (en) | 1988-03-24 |
| EP0259850B1 (en) | 1991-07-17 |
| DE3771423D1 (en) | 1991-08-22 |
| JPH07108890B2 (en) | 1995-11-22 |
| EP0259850A2 (en) | 1988-03-16 |
| EP0259850A3 (en) | 1988-09-28 |
| JPS63152350A (en) | 1988-06-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed | ||
| MKEC | Expiry (correction) |
Effective date: 20121205 |